Over the next year we will concentrate our efforts on: 1) Understanding the pathogenetic mechanisms operating in the axonal neuropathies caused by methyl-n butyl ketone and hexanedione. We will combine autoradiographic, radiometric and biochemical (gel electrophoresis) methods in our approach to this problem. 2) Evaluating the experimental neuropathy produced by iminodiproprionitrile. This compound produces pathologic changes (proximal axonal swellings) which very closely resemble those seen in human motor neuron disease, eg. ALS (Clark, Price and Griffin, in preparation). The approach will be multidisciplinary as outlined above. We have only very recently initiated studies on an animal model of motor neuron disease. This disorder of Britteny spaniels (Cork, Price and Griffin, in preparation) appears to be the most faithful animal model of motor neuron disease yet uncovered. At present, our Department of animal Medicine has three affected dogs and we have received institutional support to maintain and breed them over the next six months. The concepts and methods for studying these dogs will be derived from our studies of the experimental neuropathies.